PARP Inhibitors For Advanced Prostate Cancer
- PARP inhibitors are a newer class of oral therapies for advanced prostate cancer that target faulty DNA repair mechanisms.
- This class of drugs is particularly effective at treating cancers that have gene mutations like the BRCA mutation.
- Two PARP inhibitors, olaparib (Lynparza) and rucaparib (Rubraca), have been approved by the FDA for prostate cancer. Additional PARP inhibitors, talazoparib (Tazenna) and niraparib, have been approved to treat prostate cancer in combination with other drugs.
- Not all patients with advanced prostate cancer will benefit from PARP inhibitors. These treatments work best in individuals whose cancer cells have mutations in specific DNA repair genes, such as BRCA1, BRCA2, ATM, CHEK2, PALB2.
- If you or your doctor suspect that you may be a candidate for these drugs, ask about genetic testing.
These drugs can slow disease progression and improve outcomes for eligible patients whose cancer no longer responds to standard hormone treatments.
Read MoreA New Option For Advanced Prostate Cancer
If you or a loved one has been diagnosed with advanced prostate cancer, you may already be familiar with the journey of hormone therapy, scans, and regular blood tests. For many, initial treatment works well for a time. But what happens when the cancer stops responding to hormone therapy? This condition is known as castration-resistant prostate cancer (CRPC) and thankfully, there are promising new treatment options for patients in this situation — including PARP inhibitors.These targeted therapies are changing the landscape of prostate cancer care by focusing on the unique biology of cancer cells, and they offer new hope for patients whose cancer has spread and is no longer responding to traditional treatments.
How Do PARP Inhibitors Work?
To understand how PARP inhibitors work, it helps to understand a bit about how cells function. All cells, including cancer cells, need to be able to repair damage to their DNA in order to survive. Normally, cells use several different systems to repair that damage. One such system involves a family of proteins called PARP (poly ADP-ribose polymerase), which help fix single-strand breaks in DNA.
PARP inhibitors block this repair pathway. When a prostate cancer cell has an existing problem in another repair pathway — especially the BRCA1 or BRCA2 genes, which are involved in fixing double-strand breaks — it becomes especially vulnerable. With both pathways shut down, the cancer cell can’t repair itself effectively and eventually dies.
This concept is known as synthetic lethality — where blocking two pathways that the cancer cell relies on leads specifically to cancer cell death. Normal cells, which usually have at least one functioning DNA repair mechanism, are less affected.
Who Is Eligible For PARP Inhibitors?
Not all patients with advanced prostate cancer will benefit from PARP inhibitors. These treatments work best in individuals whose cancer cells have mutations in specific DNA repair genes, such as:
- BRCA1
- BRCA2
- ATM
- CHEK2
- PALB2
Testing for these mutations is typically done using a genomic test that analyzes either the cancer tissue or, in some cases, a blood sample. If you or your doctor suspect that you may be a candidate for these drugs, ask about genetic testing. Both germline (inherited) and somatic (acquired in the tumor) mutations can qualify a patient for treatment.
Two PARP inhibitors have been approved by the FDA for prostate cancer, including:
- Olaparib (Lynparza)
- Rucaparib (Rubraca)
Additional PARP inhibitors, talazoparib (Tazenna) and niraparib, have been approved to treat prostate cancer in combination with other drugs.
To be eligible, patients must meet certain criteria like having castration-resistant disease and mutations in certain genes.
What Are the Side Effects?
Like all cancer therapies, PARP inhibitors do come with potential side effects.
“They do have side effects and sometimes these side effects can be as strong as chemotherapy,” Dr. Sharma explains. “However, because we’ve been using these drugs for many years in breast cancer and prostate cancer, physicians have good ways of managing any side effects that you may experience.
“But, it is important to have regular follow-up while you’re on these pills,” she adds.
Most patients do tolerate the drugs reasonably well, but some people may experience side effects such as:
- Fatigue
- Nausea
- Anemia (low red blood cell count)
- Low platelets or white blood cells
- Loss of appetite or taste changes
- Abdominal discomfort or constipation
- Headache or dizziness
Your doctor will monitor your blood counts regularly and adjust your dose if necessary. In rare cases, more serious complications like myelodysplastic syndrome (MDS) or acute leukemia have been reported, though these are extremely uncommon and usually occur after long-term use.
Taking A PARP Inhibitor: What To Expect
One of the advantages of PARP inhibitors is that they are taken orally, typically as pills once or twice a day. This allows patients to take their medication from home, reducing the need for frequent hospital visits. The exact dosage and schedule depend on the specific drug and your health profile, including kidney and liver function.
It’s important to take the medication exactly as prescribed and to report any side effects to your healthcare provider promptly. Food or other medications can affect how the drug is absorbed, so be sure to follow instructions about timing and drug interactions carefully.
Risks Vs. Benefits
For patients with qualifying HRR gene mutations, PARP inhibitors can offer meaningful improvements in progression-free survival — the length of time during which the cancer does not grow or spread. Some patients experience shrinkage of tumors, a drop in PSA levels, and even improved overall survival in certain subgroups.
In clinical trials like PROfound (for olaparib), patients with BRCA1/2 or ATM mutations had significantly better outcomes than those receiving standard therapies alone. Some studies suggest that patients with BRCA2 mutations may derive the greatest benefit.
However, it’s important to understand that PARP inhibitors are not curative. They can slow the cancer’s progression, help manage symptoms, and extend life, especially when used in combination with other therapies. The response can vary significantly between individuals, so your care team will closely monitor your progress.
What Are My Other Options?
If you’re not eligible for a PARP inhibitor, or if the treatment stops working, other options are still available, such as:
- Next-generation hormone therapies (e.g., enzalutamide, abiraterone)
- Chemotherapy (typically docetaxel or cabazitaxel)
- Radiopharmaceuticals (e.g., Pluvicto, which targets PSMA-positive tumors)
- Immunotherapy, especially in patients with microsatellite instability-high (MSI-H) tumors
- Clinical trials (which test new and innovative treatment approches)
In some cases, combination therapies may be used — for example, a PARP inhibitor alongside a hormone therapy. Research is ongoing to identify which combinations work best and in which patient populations.
What Should I Do Next?
If you or someone you care about has been diagnosed with advanced prostate cancer, especially if it’s no longer responding to standard hormone therapy, talk to your oncologist about whether genetic testing is appropriate. If your cancer has mutations in certain DNA repair genes, a PARP inhibitor might be a powerful new option in your treatment plan.
As always, your cancer care should be tailored to your personal medical history, goals, and values. With the growing number of targeted therapies available, patients today have more choices than ever before—and more reason to hope.
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